Specific gene expression profiles distinguish among functional allelic variants of the mouse Pthlh gene in transfected human cancer cells

Abstract

The mouse parathyroid hormone-like hormone (Pthlh) gene encodes three allelic variants characterized by amino acid substitutions that are associated with susceptibility (PthlhPro) or resistance (PthlhThr and PthlhSerAspTyr) to two-stage skin carcinogenesis and to modulation of cell migration in vitro in transfected human cancer cells. cDNA microarray hybridization analysis of 8473 transcript clones revealed a similar gene expression profile for the PthlhThr and PthlhSerAspTyr alleles but a distinct pattern for the PthlhPro allele, suggesting an association between a specific gene expression profile and biological function of the Pthlh alleles. Some of the genes modulated by the Pthlh alleles, e.g., ANXA1, CCL2, FN1 and TFF3, play a role in cell migration and may represent candidate targets for this Pthlh function. Our study demonstrates the potential usefulness of gene expression profiling of genetic variants for the functional characterization of candidate cancer modifier genes. © 2006 Nature Publishing Group All rights reserved.